Quinolone derivatives and processes for preparing the same

ABSTRACT

PCT No. PCT/KR94/00005 Sec. 371 Date Oct. 11, 1995 Sec. 102(e) Date Oct. 11, 1995 PCT Filed Jan. 18, 1994 PCT Pub. No. WO94/15938 PCT Pub. Date Jul. 21, 1994The present invention relates to quinoline derivatives substituted in the 7-position by a trans-2,8-diazabicyclo[4.3.0]nonan-8-yl group having a broad antibacterial spectrum and to processes for preparing the same.

This application is a 371 of PCT/KR94/00005 filed Jan. 18, 1994.

TECHNICAL FIELD

The present invention relates to novel quinolone derivatives which havea broad antibacterial spectrum, and processes for preparing the same.

BACKGROUND ART

Nalidixic acid developed in 1963 is the first one of quinolonecarboxylicacid-type antibacterials. Quinolonecarboxylic acid-type antibacterialsare known to exhibit strong antibacterial activity against aerobicGram-negative bacteria and have been effectively used as a treatment forurethritis. Among these quinolone carboxylic acid-type antibacterials,especially norfloxacin, ciprofloxacin, of loxacin, etc. are clinicallyused. However, these prior art compounds suffer from the disadvantagethat they have drastically inferior antibacterial activity againstGram-positive bacteria, while they have superior antibacterial activityagainst Gram-negative bacteria. Especially, these quinolone-typeantibacterials are known to have weak antibacterial activity againstGram-positive bacteria such as Staphylococcus or Enterococcus which showhigh resistance to sepem-type or β-lactam-type antibacterial agents.

DISCLOSURE OF INVENTION

The present invention provides novel quinolone derivatives of formula(I), (III) and (IV) below and processes for preparing the same. ##STR1##wherein, X₁ represents hydrogen, amino group, halogen such as chloro,fluoro, or lower alkyl such as methyl;

X₂ represents hydrogen or halogen;

Y₁ and Y₂ each represents hydrogen, or lower alkyl (C₁₋₃) group;

R₁ represents a straight chain or cyclic lower alkyl group having 1 to 3carbon atoms or a straight chain or cyclic lower alkyl group having 1 to3 carbon atoms which is substituted with a halogen atom, a phenyl groupor a phenyl group substituted with one or two halogen atoms;

R₂ represents hydrogen, or lower alkyl such as methyl, ethyl;

R₃ and R₄ each represent hydrogen, nitro group, methoxycarbonyl group,ethoxycarbonyl group or nitryl group; and

A represents nitrogen atom or ##STR2## in which Y represents hydrogen,halogen, lower alkyl or alkoxy or together with R₁ forms --CH₂ CH₂ CH₂--, --CH₂ CH₂ CH(CH₃)--, --OCH₂ CH₂ --, --OCH₂ CH(CH₃)--, --SCH,CH₂ --,or --SCH₂ CH(CH₃)--.

A is preferably nitrogen, methyn, fluoromethyn, chloromethyn,methoxymethyn, or methylmethyn.

Lower alkyl is preferably C₁₋₆ alkyl, more preferably C₁₋₄ alkyl, suchas methyl or ethyl. X₂ halogen is preferably fluorine.

R₁ is preferably ethyl, cyclopropyl, halogen (F, Cl)-substitutedcyclopropyl or halogen substituted phenyl.

The present invention is described in detail hereinbelow.

The present invention provides novel quinolone carboxylic acidderivatives of formula (I), and specifically, to novel quinolonecarboxylic acid derivatives of formula (I) below which havetrans-2,8-diazabicyclo 4.3.0!nonane derivatives represented by theformula (II) at 7-position of quinolone nucleus and possess a broadspectrum of potent antibacterial activities, and to processes forpreparing the same. ##STR3## wherein, X₁, X₂, Y₁, Y₂, R₁, R₂, and A arethe same as defined above.

The present invention also provides novel quinolone carboxylic acidderivatives represented by the formula (III) and (IV) including mixturesthereof which show a broad spectrum of potent antibacterial activities,and to processes for preparing the same. ##STR4## wherein, X₁, X₂, Y₁,Y₂, R₁, R₂, R₃, R₄, and A are the same as defined above.

The present invention provides trans-2,8-diazabicyclo 4.3.0!nonanederivatives represented by the formula (II) which are used as a sidechain at 7-position of novel quinolone carboxylic acid derivatives (I)and processes for preparing the same. ##STR5## wherein, Y₁, Y₂, and R₂are the same as defined above.

The present invention also provides novel processes for preparingcis-2,8-diazabicyclo 4.3.0!nonane derivatives represented by thefollowing formula (V) which are used as a side chain at 7-position offormula (IV) above. ##STR6## wherein, Y₁ and R₂ are the same as definedabove.

Quinolone derivatives of formula (I) according to the present inventionmay be prepared by condensing optionally protectedtrans-2,8-diazabicyclo 4.3.0!nonane derivatives of formula (II) abovewith the known compound of formula (VI-1) (P. D. Fernandes,"International Telesymposium on Quinolone", J. R. Prous Science,Barcelona, Spain, 1989. 1-143) in a solvent, in the presence of aninorganic or organic base, as described in the process (A). Inorganicbases used in this process include potassium carbonate and the like.Organic base used herein include diazabicyclo 5.4.0!undecene (DBU),pyridine, triethylamine and the like. The above reaction may be carriedout at a temperature between room temperature and 150° C. The reactiontime is about 1 to 10 hours. ##STR7## wherein, X₁, X₂, Y₁, Y₂, R₁, R₂,and A are the same as defined above or R₂ is a protecting group such ast-butoxy carbonyl which is removed subsequently.

Also, quinolone derivatives represented by formula (III) of the presentinvention may be prepared by the following process (B). That is, thecompound of formula (III) can be prepared by stirring compound offormula (I) and an activating agent such as carbodiimidazole (CDI) underreflux in the presence of a solvent such as chloroform, tetrahydrofuran(THF) and the like and then stirring nitromethane, diethylmalonate,dimethylmalonate, ethylnitrylacetate under reflux together with solutiontreated with a base such as sodium hydride, calcium carbonate, sodiumcarbonate in the presence of a solvent such as THF, and the like.##STR8## wherein, X₁, X₂, Y₁, Y₂, R₁, R₂, R₃, and R₄ are the same asdefined above; and represent nitro group, nitryl group, diethoxycarbonylgroup, or dimethoxycarbonyl group, and thereafter optionallyinterconverting R₃ and R₄.

Quinolone derivatives represented by formula (IV) of the presentinvention may be prepared by the following process (C). That is, thecompound of formula (IV) can be prepared by reacting optionallyprotected cis-2,8-diazabicyclo 4.3.0!nonane derivatives of formula (V)with the compound of formula (IV-2) under reflux stirring in a solventof acetonitrile or dimethylformamide (DMF) in the presence of basic,neutral, or acidic alumina. ##STR9## wherein, X₁, X₂, Y₁, R₁, R₂, R₃,and A are the same as defined above or R₂ is a protecting group such ast-butoxy carbonyl which is removed subsequently.

Novel quinolone derivatives of formula (IV) above can be also preparedby stirring the condensed compound with the solution under reflux. Thecondensed compound may be prepared by reacting cis-2,8-diazabicyclo4.3.0!nonane derivatives of formula (V) with the known compound offormula (VI-2) in a solvent in the presence of an organic or inorganicbase. Organic base used herein include diazabicyclo 5.4.0!undecene(DBU),pyridine, triethylamine and the like. Inorganic bases used in thisprocess include potassium carbonate and the like. The above reaction maybe carried out at a temperature between room temperature and 150° C. Thereaction time is about 1 to 10 hours. The above solution is prepared bystirring carbodiimidazole under reflux in a solvent such as chloroform,tetrahydrofuran, and then stirring nitromethane, diethylmalonate,dimethylmalonate, ethylnitrylacetate under reflux with a base such assodium hydride, calcium carbonate, sodium carbonate in a solvent such astetrahydrofuran and the like.

The compounds of formula (I), (III) and (IV) above can be converted tothe pharmaceutically acceptable salts thereof according to theconventional method. For example, these compounds can be converted tosalts of inorganic acid such as hydrochloric acid, sulfuric acid, andphosphoric acid or salts of organic acid such as methansulfonic acid,lactic acid, oxalic acid, and acetic acid.

Trans-2,8-diazabicyclo 4.3.0!nonane derivatives of the following formula(II) according to the present invention can be prepared by the followingProcess (D). The Process(D) comprises the following four steps:

Step (1)

The compound of formula (VIII) can be prepared by reacting the knowncompound of formula (VII) (J.Org.Chem. 48, 1129 (1983)) with β-alaninederivatives in the presence of ethanol under reflux;

Step (2)

The compound of formula (IX) can be prepared by cyclizating the compoundof formula (VIII) with alkoxide such as sodium ethoxide or potassiumt-butoxide at room temperature in the aromatic solvent such as benzene,toluene;

Step (3)

The compound of formula (X) can be prepared by reacting the carbonylcompound of formula (IX) with tosylhydrazine in a solvent of ethanol ormethanol to obtain tosylhydrazone and then, by reducing the resultingcompound with sodium shanobrohydride; and

Step (4)

The compound of formula (II) can be prepared by debenzylating thecompound of formula (X) in methanol solvent in the presence of acatalyst of palladium or platinum. ##STR10## wherein, Y₁, Y₂, and R₂ arethe same as defined above.

Trans-2,8-diazabicyclo 4.3.0!nonane derivatives of the following formula(II) according to the present invention can also be prepared by thefollowing Process (E). The Process(E) comprises the following sevensteps:

Step (5)

Trans isomer of formula (XIII) can be prepared by reacting the knowncompound of formula (XII) (UK Patent No. 1,086,637, or ChemicalAbstract, 68, 96695W) with β-alanine derivatives in the presence ofethanol under reflux;

Step (6)

Cis isomer of formula (XIV) can be prepared by reacting trans isomer offormula (XIII) with methansulfonyl chloride or lithium chloride, inmethylene chloride or chloroform, in the presence of an organic basesuch as triethylamine or diisopropylethylamine, at the temperaturebetween 0° C. and 60° C.;

Step (7)

Trans isomer of formula (XV) can be prepared by reacting cis isomer offormula (XIV) with potassium cyanate or sodium cyanate in DMF solvent;

Steps (8) and (9)

The compound of formula (IX) can be prepared from the compound offormula (XV) by the same method as Step (2) of Process (D) above;

Step (10)

The compound of formula (X) can be prepared by reducing the compound offormula (IX) with zinc amalgam in the presence of hydrochloric acid; and

Step (11)

The compound of formula (II) can be prepared from the compound offormula (X) by the same method as Step (4) of Process (D) above.##STR11## wherein, Y₁, Y₂ and R₂ are the same as defined above.

Cis-2,8-diazabicyclo 4.3.0!nonane derivatives of the formula (V)according to the present invention can be prepared by the followingProcess (F). The Process(D) comprises the following seven steps:

Step (12)

The ester compound of formula (XVIII) can be prepared by suspendingconventional pyridine derivatives of formula (XVII) in methanol andadding thionylchloride thereto and then stirring the resulting compoundunder reflux;

Step (13)

Alcohols of formula (XIX) can be prepared by reducing the compound offormula (XVIII) with lithium aluminum hydride in ethylether or THF;

Step (14)

The compound of formula (XX) can be prepared by chlorinating,brominating, or methane sulfonylating alcohols of formula (XIX);

Step (15)

The cyclized compound of formula (XXI) can be prepared by reacting thecompound of formula (XX) with tocylimide and sodiumhydride in DMF;

Step (16)

Amines of formula (XXII) can be prepared by hydrolyzing the compound offormula (XXI) with 48% of hydrobromic acid;

Step (17)

Salts of pyridine of formula (XXIII) can be prepared by reacting aminecompounds of formula (XXII) with methaneiodide and acid anhydrous in asolvent of methylene chloride or ethyl alcohol; and

Step (18)

Cis-2,8-diazabicyclo 4.3.0!nonane derivatives of formula (V) can beprepared by hydrogenating the compound of formula (XXIII) in a solventof methanol or ethanol in the presence of a catalyst of palladium orplatinum. ##STR12## wherein, X₃ represents chloro, bromo, ormethanesulfonyloxy group; and

Y₁ and R₂ are the same as defined above.

The following examples are intended to further illustrate the presentinvention, without limiting the scope of the invention.

EXAMPLE 1 Preparation of trans-piperidinopyrrolidine

1) Preparation according to Process (D)

i) Preparation of trans-1-benzyl-3-carboethoxy-4-N-benzyl-N-(2-carboethoxy)ethyl!aminopyrrolidine

A mixture of 23.9 g of 1-benzyl-3-ethoxycarbonyl-3-pyrroline and 19.2 gof β-N-benzylalanine ethylester were added to 100 ml of ethanol andstirred under reflux for 3 days. The solvent was evaporated underreduced pressure and then the residual product was purified by a silicagel column chromatography (nucleic acid-ethylacetate (3:1)) to give 26.9g of the above title compound (yield: 65%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 2.21(2H, m), 2.51(2H, m), 3.10-4.01(6H, m), 3.71(6H, s),7.25(10H, m)

ii) Preparation of trans-N,N'-dibenzyl-2,8-diazabicyclo4.3.0!-5-oxononane

20.5 g of trans-1-benzyl-3-carboethoxy-4- N-benzyl-N(2carboethoxy)ethyl!aminopyrrolidine was dissolved in 200 ml of toluene and thereaction mixture was cooled in ice bath and then 6.1 g of potassiumt-buthoxide was added dropwise thereto. After adding dropwise, thereaction mixture was heated to 40° C. and stirred for 4 hours. Thereaction mixture was evaporated under reduced pressure and the residuewas dissolved in water. The resulting product was neutralized withaqueous solution of sodium bicarbonate, extracted with ethylacetate andthen dried with anhydrous magnesium sulfate. The solvent was evaporatedunder reduced pressure and then the residual product was purified by asilica gel column chromatography to give 11.8 g of the above titlecompound (yield: 71%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 2.30-3.0(9H, m), 3.20-3.70(2H, q), 3.50(6H, s), 3.4(1H, q), 7.15(10H, m)

iii) Preparation of trans-N,N'-dibenzylpiperidinopyrrolidine

15.9 g of trans-N,N'-dibenzyl-2,8-diazabicyclo 4.3.0!-5-oxononane and9.3 g of tosyl hydrazine was added to 100 ml of ethanol and thendehydrated with Dean-Stark distillation apparatus. 14 g of sodiumborohydride was added thereto and the mixture was stirred for 4 hours.The solvent was evaporated under reduced pressure and then the residuewas extracted with ethylether. The mixture of ethylether was evaporatedunder reduced pressure and then the residual product was purified by asilica gel column chromatography (nucleic acid-ethylacetate (3:1)) togive 13.2 g of the above title compound (yield: 87%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 1.54-2.01(5H, m), 2.74-3.10(7H, m), 3.20-3.70(4H, m) 7.30(10H, m)

iv) Preparation of trans-piperidinopyrrolidine dihydrochloride

13.15 g of trans-N,N'-dibenzylpiperidinopyrrolidine were dissolved in 50ml of methanol and then 1.0 g of 10% Pd/C and 60 ml of 30% methanol wereadded thereto. The resulting solution was hydrogenated by Parrhydrogenation reactor and debenzylated. The reaction mixture wasfiltered through celite and the filtrate was evaporated under reducedpressure. The residue was dissolved in 10 ml of methanol and ethyletherwas added dropwise to the mixture. The resulting mixture was solidifiedand filtered to give 7.43 g of the above title compound (yield: 93%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 1.50-190(5H, m), 2.74-3.01(7H, m)

2) Preparation according to Process (E)

i) Preparation of trans-1-benzyl-3-hydroxy-4-N-benzyl-N-(2-carboethoxy)ethyl!aminopyrrolidine

87.25 g (0.5 mol) of 3-benzyl-6-oxy-3-azabicyclo 3.1.0!nucleic acid and113.8 g (0.51 mol) of 3N-benzylaminopropanoate were put into 200 ml ofpyridine and stirred under reflux for 3 days. The reaction mixture wasevaporated under reduced pressure to remove pyridine and then theresidue was subjected to a silica gel column chromatography (nucleicacid-ethylacetate (1:1)) to give 166.2 g of the above title compound(yield: 87%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 1.26(3H, t), 2.24(2H, m), 2.50(2H, m), 3.90(1H, m), 3.10-4.0(9H, m), 4.20(2H, q), 7.23(10H, m)

ii) Preparation of cis-1-benzyl-3-chloro-4-N-benzyl-N-(2-carboethoxy)ethyl!aminopyrrolidine

95.5 g (0.25 mol) of trans-1-benzyl-3-hydroxy-4-N-benzyl-N-(2-carboethoxy) ethyl!aminopyrrolidine and 70 ml oftriethylamine were dissolved in 11 of methylene chloride and 31.4 g ofmethane sulfonyl chloride were added dropwise thereto at 0° C. 21.3 g ofanhydrous lithium chloride were added to the mixture and the reactionmixture was heated to 60° C. and stirred for 20 hours. The reactionmixture was cooled, washed with water and dried over anhydrous magnesiumsulfate. After the solvent was evaporated under reduced pressure, theresidue was purified by a silica gel column chromatography (nucleicacid-ethylacetate (3:1)) to give 80.15 g of the above title compound(yield: 82%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 1.26(3H, t), 2.24-2.52(4H, m), 3.10-4.0(9H, m), 4.14(1H,m),4.20(2H, q), 7.30(10H, m)

iii) Preparation of trans-1-benzyl-3-cyano,-4-N-benzyl-N-(2-carboethoxy)ethyl!aminopyrrolidine

40.1 g (0.1 mol) of trans-1-benzyl-3-chloro-4-N-benzyl-N-(2-carboethoxy)ethyl!aminopyrrolidine and 7.8 g of potassiumcyanate were put into 100 ml of DMF and the mixture was heated at 60° C.for 14 hours while stirring. The reaction mixture was added to 400 ml ofice water while stirring and the produced solid was filtered. Theresulting solid was dissolved in ethylacetate and then the mixture wassubjected to a silica gel column chromatography (nucleicacid-ethylacetate (3:1)) to give 30.5 g of the desired compound (yield:78%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 1.27(3H, t), 2.24(2H, m), 2.50(2H, m), 3.10-4.0(9H,m),4.20(2H, q), 7.30(10 H, m)

iv) Preparation of trans-1-benzyl-3-carboethoxy-4-N-benzyl-N-(2-carboethoxy)ethyl!aminopyrrolidine

30.0 g of trans-1-benzyl-3-cyano-4-N-benzyl-N-(2-carboethoxy)ethyl!aminopyrrolidine were put into 300 ml of10% hydrochloric acid and the mixture was refluxed for 6 hours. Afterwater was evaporated under reduced pressure, the residue was heated anddried in vacuum drier for 10 hours. The residue was suspended in 200 mlof methanol and 30 ml of thionylchloride was added dropwise to themixture while refluxing and further refluxed for 5 hours. The reactionmixture was evaporated under reduced pressure, the residue was put intomethanol and 11 g of sodium methoxide was added gradually thereto at 0°C. The resulting mixture was evaporated under reduced pressure again,dissolved in ethylacetate and washed with water. The organic layer wasdried over anhydrous magnesium sulfate and evaporated under reducedpressure, and the residue was subjected to a silica gel columnchromatography (nucleic acid-ethylacetate (3:1)) to give 30.5 g of thetitle compound (yield: 61%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 2.21(2H, in), 2.51(2H, m), 3.10-4.01(6H, m), 3.71(6H, s),7.25(1OH, m)

v) Preparation of trans-N,N'-dibenzyl-2,8-diazabicyclo4.3.0!-5-oxononane

20.5 g of trans-1-benzyl-3-carboethoxy-4-N-benzyl-N-(carboethoxy)ethyl!aminopyrrolidine was dissolved in 200 mlof toluene and the reaction mixture was cooled in ice bath and then 6.1g of potassium t-buthoxide was added dropwise thereto. After addingdropwise, the reaction mixture was heated to 40° C. and stirred for 4hours. The reaction mixture was evaporated under reduced pressure andthe residue was dissolved in water. The resulting product wasneutralized with aqueous solution of sodium bicarbonate, extracted withethylacetate and then dried over anhydrous magnesium sulfate. Thesolvent was evaporated under reduced pressure and then the residualproduct was purified by a silica gel column chromatography to give 11.8g of the above title compound (yield: 74%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 2.30-3.0(9H, m), 3.20-3.70(2H, q), 3.50(6H, s), 3.4(1H, q),7.15(10H, m)

vi) Preparation of trans-N, N'-dibenzyl-piperidinopyrrolidine

6.5 g of zinc powder were put into 15 ml of aqueous solution of 5% HgCl₂and the mixture solution was shaken for 1 hour. The supernatant wasremoved and 9.6 g of N,N'-dibenzyl-2,8-diazabicyclo 4.3.0!-5-oxononanewas added thereto. 10 ml of 15% hydrochloric acid was added and thesolution was heated while refluxing for 6 hours. While refluxing, 10 mlof 5% hydrochloric acid was added several times. The mixture was cooledand 40 ml of ethylacetate was added thereto and then supernatant of themixture was removed. The suspension was filtered and the filtrate wasneutralized with 5% KOH and extracted with ethylacetate. The extractedsolution was dried over anhydrous magnesium sulfate. The solvent wasevaporated under reduced pressure and then the residual product waspurified by a silica gel column chromatography (nucleicacid-ethylacetate (3:1)) to give 7.44 g of the above title compound(yield: 81%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 1.54-2.01(5H, m), 2.74-3.10(7H, m), 3.2-3.70(4H, m),7.30(10H, m)

vii) Preparation of trans-piperidinopyrrolidine dihydrochloride

6.12 g (0.02 mol) of trans-N,N'-dibenzyl-piperidinopyrrolidine weredissolved in 30 ml of methanol and then 0.5 g of 10% Pd/C and 5 ml offumaric acid were added thereto. The resulting solution was hydrogenatedby Parr hydrogenation reactor (initial hydrogen pressure: 60 psi) todebenzylate. The reaction mixture was filtered through celite and thefiltrate was evaporated under reduced pressure. The residue wasdissolved in 10 ml of 30% hydrochloride methanol and ethylether wasadded dropwise to the mixture. The resulting mixture was solidified andfiltered to give 3.62 g of the above title compound (yield: 92%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 1.50-1.90(5H, m), 2.74-3.01(7H, m)

EXAMPLE 2 Preparation of trans-3-methyl-piperidinopyrrolidinedihydrochloride

According to the same method as i), ii), iii), iv), v), vi) and vii) ofProcess (E) in Example 1, 121 g of methyl-3-(N-benzyl)aminobutanoate asa starting material was used to give 22.9 g of the above title compound(total yield: 10.1%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 1.42-1.90(7H, m), 2.74-3.01(7H, m)

EXAMPLE 3 Preparation of cis-piperidinopyrrolidine dihydrobromide

1) Preparation of 2,3-dimethoxycarboylpyridine

26.7 g of 2,3-pyridinedicarboxylic acid were put into 500 ml of methanolsaturated with hydrogen chloride and the mixture was refluxed for 10hours. Methanol was evaporated under reduced pressure and then theresidual product was purified by a silica gel column chromatography(nucleic acid-ethylacetate (1:1)) to give 25.1 g of the above pure titlecompound (yield: 85%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 3.95(6H, s), 7.34(1H, m), 7.51(1H, d), 8.84(1H, d)

2) Preparation of 2,3-dihydroxymethylpyridine

A solution prepared by dissolving 29.5 g, of2,3-dimethoxycarbonylpyridine in 200 ml of ethylether was added dropwiseto a solution prepared by suspending 10 g of lithium aluminum hydride in300 ml of dried ethylether at 0° C. This mixed solution was stirred at20° C. for 3 hours and 30 ml of water was slowly added thereto at 0° C.The resulting solution was stirred for 5 hours at the room temperatureand solid was filtered through celite. The filtrate was evaporated underreduced pressure and then the residual product was purified by a silicagel column chromatography (chloroform : methanol (10:1)) to give 10.4 gof the above title compound (yield: 75%).

    .sup.1 H-NMR(CDCl.sub.3 +DMSO-d.sub.6, δ): 4.58(2H, d), 4.67(2H, d), 5.13(1H, s), 5.30(1H, s), 7.34(1H, m), 7.45(1H, d), 8.45(1H, d)

3) Preparation of 2,3-dichloromethylpyridine hydrochloride

13.9 g of 2,3-dihydroxymethylpyridine and thionylchloride wereevaporated under reduced pressure to give 21.2 g of the above titlecompound in yellow solid (yield: 99%).

    .sup.1 H-NMR(CDCl.sub.3 +DMSO-d.sub.6, δ): 5.10(2H, s), 5.15(2H, s), 7.81(1H, m), 8.15(1H, m), 8.15(1H, d), 8.95(1H, d)

4) Preparation of 2,3-dihydro-2-p-toluene sulfonyl-1H-pyrrolo2.3.c!pyridine

A solution prepared by suspending 0.9 g of 60% sodiumhydride in 50 ml ofdried dimethylformamide was slowly added dropwise over 2 hours to asolution prepared by dissolving 3.5 g of p-toluenephosphenylamide in 20ml of dried dimethylformamide. The reacting mixture was stirred for 1hour at the room temperature and then stirred again for 1 hour at thetemperature between 65 and 70° C. A solution prepared by dissolving 2.13g of 2,3-dichloromethylpyridine in 3 ml of dried dimethylformamide wasadded to the reaction mixture. The resulting mixture was stirred for 3hours at the same temperature and 20 ml of water was added thereto. Thesolvent was evaporated off under reduced pressure. 20 ml of water wasadded again to the mixture, and the resulting mixture was saturated withsodium hydroxide and extracted with 100 ml of ethylacetate. Theextracted solution was dried over anhydrous magnesium sulfate. Thesolvent was evaporated under reduced pressure and then the residualproduct was purified by a silica gel column chromatography (nucleicacid-ethylacetate (1:2)) to give 1.8 g of the above title compound(yield: 65%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 2.45(3H, s), 4.65-4.68(4H, d), 7.15(1H, m), 7.35(3H, d,d), 7.81(2H, m), 8.46(1H, d)

5) Preparation of 2,3-dihydro-1H-pyrrolo 2.3.c!pyridine dihydrobromide

74 g of 2,3-dihydro-2-p-toluene sulfonyl-1H-pyrrolo 2.3.c.!pyridine wasput into 20 ml of 48% hydrobromide, and 1.75 g of phenol and 9.18 ml ofpropionic acid was added thereto and then the reaction mixture wasrefluxed for 48 hours. The reaction mixture was evaporated under reducedpressure and 30 ml of water was added to. The water layer was washedwith ethylacetate and then water soluble layer was concentrated andstood in a refrigerator to give 2.23 g of the above title compound(yield: 79%).

    .sup.1 -NMR(DMSO-d.sub.6, δ): 5.24(4H, δ), 7.85(1H, m), 8.20(1H, d), 8.90(1H, d)

6) Preparation of cis-piperidinopyrrolidine dihydrobromide

1.42 g of 2,3-dihydro-1H-pyrrolo 2.3.c!pyridinehydrobromide wasdissolved in 30 ml of methanol and the mixture was suspended with 1 g of10% Pd/C. The resulting solution was hydrogenated by Parr hydrogenationreactor (initial hydrogen pressure: 60 psi) to debenzylate. After thereaction was finished, the reaction solution was filtered through celiteand the solvent was evaporated in vacuo to give 1.42 g of the abovetitle compound (yield: 99%).

    .sup.1 H-NMR(DMSO-d.sub.6, δ): 1.51-1.94(5H, m), 2.71-3.12(7H, m)

EXAMPLE 4 Preparation of cis-3-methyl-piperidinopyrrolidinedihydrobromide

According to the same method as i), ii), iii), iv), v) and vi) ofExample 3, 28.1 g of 5-methyl-2,3-dicarboxypyridine was used to give8.88 g of the above title compound (total yield: 30%).

    .sup.1 H-NMR(DMSO-d.sub.6, δ): 1.2(4H, m), 1.50-1.91(5H, m), 2.74-3.01(7H, m), 4.10(1H, m), 7.7(1H, dxd), 8.6(1H, s)

EXAMPLE 5 Preparation of 1-cyclopropyl-6-fluoro-7-(trans-piperidinopyrrolidine)-8-yl!-8-chloro-1,4-dihydroguinoline-4-oxo-3-carboxylicacid

300 mg of1-cyclopropyl-6,7-difluoro-1,4-dihydroquinoline-4-oxo-3-carboxylic acidand 210 mg of trans-piperidinopyrrolidine dihydrochloride were suspendedin 10 ml of anhydrous acetonitrile and 0.18 ml of DBU was added thereto.The reaction mixture was refluxed for 6 hours and cooled to the roomtemperature. The produced solid was filtered and washed withacetonitrile to give 405.5 mg of the above title compound (yield: 100%).

    .sup.1 H-NMR(DMSO-d.sub.6, δ): 1.22(4H, m), 1.61-2.01(5H, m), 2.74-3.01(7H, m), 4.08(1H, m), 7.56(1H, dxd), 8.61(1H, s)

EXAMPLE 6 Preparation of 1-cyclopropyl-6.8-difluoro-7-(trans-piperidinopyrrolidine)-8-yl!-1,4-dihydroquinoline-4-oxo-3-carboxylicacid

283 mg of1-cyclopropyl-6,7,8-trifluoro-1,4-dihydroquinoline-4-oxo-3-carboxylicacid and 210 mg of trans-piperidinopyrrolidine dihydrochloride weretreated according to the same method as that of Example 5 to give 327 mgof the above title compound (yield: 84%).

    .sup.1 H-NMR(DMSO-d.sub.6, δ): 1.2(4H, m), 1.50-1.91(5H, m), 2.74-3.01(7H, m), 4.10(1H, m), 7.7(1H, dxd), 8.6(1H, s)

Following compounds may be prepared by the process similar to thatdescribed in Example 5.

1-cyclopropyl-6-fluoro-7-(trans-piperidinopyrrolidine)-8-yl!-1,4dihydroquinoline-4-oxo-3-carboxylicacid;

1-cyclopropyl-5-amino-6,8-difluoro-7-(trans-piperidinopyrrolidine)-8-yl!-1,4-dihydroquinoline-4-oxo-3-carboxylicacid;

1-cyclopropyl-5-methyl-6-fluoro-7-(trans-piperidinopyrrolidine)-8-yl!-1,4-dihydroquinoline-4-oxo-3-carboxylicacid;

1-cyclopropyl-6-fluoro-7-(trans-piperidinopyrrlidine)-8-yl!-8-methoxy-1,4-dihydroquinoline-4-oxo-3-carboxylicacid;

1-cyclopropyl-6-fluoro-7-(trans-piperidinopyrrolidine)-8-yl!-1,4-dihydro-4-oxo-1,8-naphthyridin-3-carboxylicacid;

1-(2,4-difluorophenyl)-6-fluoro-7- (trans-piperidinopyrrolidine)-8-yl!-1,4-dihydro-4-oxo-1,8-naphthyridin-3-carboxylic acid;

9-fluoro- 10-(trans-piperidinopyrrolidine)-8-yl!-2,3-dihydro-3-methyl-7-oxo-7H-pyrido1,2,3-de! 1,4!-benzooxazine-6-carboxylic acid;

1-cyclopropyl-6,8-difluoro-7- (3-methyl-2,8-diazabicyclo4.3.0!nonane)-8-yl!-1,4-dihydroquinoline-4-oxo-3-carboxylic acid;

1-cyclopropyl-6-fluoro-7- (trans-3-methyl-2,8-diazabicyclo4.3.0!nonane)-8-yl!-8-chloro-1,4-dihydroquinoline-4-oxo-3-carboxylicacid;

1-cyclopropyl-5-amino-6,8-difluoro-7- (trans-3-methyl-2,8-diazabicyclo4.3.0!nonane)-8-yl!-8-methoxy-1,4-dihydroguinoline-4-oxo-3-carboxylicacid;

1-cyclopropyl-5-methyl-6-fluoro-7- (trans-3-methyl-2,8-diazabicyclo4.3.0!nonane)-8-yl!-1,4-dihydroquinoline-4-oxo-3-carboxylic acid;

1-cyclopropyl-6-fluoro-7- (trans-3-methyl-2, 8-diazabicyclo4.3.0!nonane)-8-yl!-8-methoxy-1,4-dihydroquinoline-4-oxo-3-carboxylicacid;

1 -cyclopropyl-6-fluoro-7- (trans-3-methyl-2,8-diazabicyclo4.3.0!nonane)-8-yl!-1,4-dihydro-4-oxo-1,8-naphthyridin-3-carboxylicacid; and

9-fluoro-10- (trans-3-methyl-2,8-diazabicyclo4.3.0!nonane)-8-yl!-2,3-dihydro-3-methyl-7-oxo-7H-pyrido 1,2,3-de!1,4!-benzooxazine-6-carboxylic acid.

EXAMPLE 7 Preparation of1-cyclopropyl-3-nitroacetyl-6-fluoro-8-chloro-7-(trans-piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinolinehydrochloride

183 mg of nitromethane was dissolved in 10 ml of tetrahydrofuran and 120mg of 60% NaH was suspended in the mixture. The resulting solution wasstirred for 3 hours at 40° C. 403.5 mg of1-cyclopropyl-6-fluoro-8-chloro-7-(trans-2-(N-t-butoxycarbonyl)piperidinopyrrolidine)-8-yl!-oxo-1,4-dihydroquinoline-3-carboxylic acid, 324 mg of CDI and 10 ml ofchloroform were put into the above solution. The resulting solution wasstirred under reflux for 12 hours and the solvent was evaporated underreduced pressure. The produced residue was added to 10 ml of THF and themixture was stirred under reflux for 4 hours. The reaction solvent wasevaporated under reduced pressure and the residue was suspended in 20 mlof water. The suspension was neutralized with acetic acid and extractedwith ethylacetate (20 ml ×3). The extracted solution was dried overanhydrous magnesium sulfate and the solvent was evaporated under reducedpressure. The produced residue was purified by column chromatography(CHCl₃ : MeOH=9 : 1) to give 389 mg of1-cyclopropyl-3-nitroacetyl-6-fluoro-8-chloro-7-(trans-2-(N-t-butoxycarbonyl)piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinoline.This compound was put into 5 ml of 10% methanol solution of hydrogenchloride and the mixture was stirred for 4 hours at room temperature andthen 5 ml of ethylether was added thereto. The produced solid wasfiltered and dried under reduced pressure to give 335 mg of the abovetitle compound (yield: 64%).

    .sup.1 H-NMR(DMSO-d.sub.6, δ): 1.22(4H, m), 1.01-1.98(5H, m), 2.78-3.08(7H, m), 4.06(1H, m), 6.18(2H, s), 7.74(1H, dxd), 8.78(1H, s)

EXAMPLE 8 Preparation of1-cyclopropyl-3-nitroacetyl-6-fluoro-8-methoxy-7-(trans-piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinolinehydrochloride

497 mg of 1-cyclopropyl-6-fluoro-8-methoxy-7- (trans-2-(N-t-butoxycarbonyl)piperidinopyrrolidine)-8-yl!-oxo-1,4-dihydroquinoline-3-carboxylic acid were treated according to thesame method as that of Example 7 to give 327 mg of the title compound(yield: 74%).

    .sup.1 H-NMR(DMSO-d.sub.6, δ): 1.20(4H, m), 1.51-1.91(5H, m), 2.70-3.04(7H, m), 3.86(3H, s), 4.00(1H, m), 6.16(2H, s), 7.86(1H, d), 8.84(1H, s)

Following compounds may be prepared by the process similar to thatdescribed in Example 7.

1-cyclopropyl-3-nitroacetyl-6,8-difluoro-7-(trans-piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinolinehydrochloride;

1-cyclopropyl-3-nitroacetyl-5-amino-6,8-difluoro-7-(trans-piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinolinehydrochloride;

1-(2,4-difluoro)phenyl-3-nitroacetyl-6-fluoro-7-(trans-piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydro- 1,8-naphthyridinehydrochloride;

1-cyclopropyl-3-nitroacetyl-6,8-difluoro-7- (trans-2,8-diazabicyclo4.3.0!nonane-3-methyl)-8-yl!-4-oxo-1,4-dihydroquinoline hydrochloride;and

1-cyclopropyl-3-(diethoxycarbonyl)acetyl-6,8-difluoro-7-(trans-piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinolinehydrochloride.

1-cyclopropyl-3-(dimethoxycarbonyl)acetyl-6-fluoro-8-methoxy-7-(trans-piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinolinehydrochloride.

EXAMPLE 9 Preparation of1-cyclopropyl-3-nitroacetyl-6-fluoro-8-methoxy-7-(cis-piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinolinehydrochloride

1) Preparation according to Process (B)

497 mg of 1-cyclopropyl-6-fluoro-8-methoxy-7-(cis-2-(N-t-butoxycarbonyl)piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinoline-3-carboxylicacid were treated according to the same method as that of Example 7 togive 314 mg of the above title compound (yield: 71%).

    .sup.1 H-NMR(DMSO-d.sub.6, δ): 1.18(4H, m), 1.57-2.00(5H, m), 2.70-3.04(7H, m), 3.86(3H, s), 4.00(1H, m), 6.18(2H, s), 7.86(1H, d), 8.84(1H, s)

2) Preparation according to Process (C)

i) Preparation of1-cyclopropyl-3-nitroacetyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline

566 mg of1-cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylicacid and 648 mg of CDI were put into 20 ml of THF and the mixturesolution is stirred under reflux for 24 hours (A solution). 366 mg ofnitromethane was mixed in 5 ml of THF and 240 mg of 60% NaH addedthereto. The mixture solution was stirred for 24 hours at roomtemperature and the above A solution was added thereto. The resultingsolution was stirred under reflux for 14 hours. The reaction mixture wascooled and the solvent was evaporated under reduced pressure. Theproduced residue was purified by column chromatography (nucleic acid:ethylacetate =5 : 1) to give 450 mg of the above title compound (yield:69%).

    .sup.1 H-NMR(DMSO-d.sub.6, δ): 1.20(4H, m), 3.62(3H, s), 4.00(1H, m), 6.12(2H, s), 7.67(1H, d), 8.60(1H, s)

ii) Preparation of 1-cyclopropyl-3-nitroacetyl-6-fluoro-8-methoxy-7-(cis-piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinolinehydrochloride

338 mg of1-cyclopropyl-3-nitroacetyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinolineand 310 mg of cis-piperidinopyrrolidine were dissolved in 10 ml ofacetonitrile. 310 mg of alumina were added thereto and the mixture wasstirred for 10 hours at 60° C. The reaction mixture was evaporated underreduced pressure and the produced residue was suspended in methanol andthe mixture solution was stirred under reflux and filtered. The filtratewas collected and evaporated under reduced pressure. The producedresidue was put into 15 ml of 10% solution of HCl-methanol and themixture solution was stirred for 2 hours at room temperature. 15 ml ofethylether was added thereto and the resulting solution was filtered togive 296 mg of the above title compound (yield: 67%).

    .sup.1 H-NMR(DMSO-d.sub.6, δ): 1.18(4H, m), 1.57-2.00(5H, m), 2.70-3.04(7H, m), 3.86(3H, s), 4.00(1H, m), 6.18(2H, s), 7.86(1H, d), 8.84(1H, s)

Following compounds may be prepared by the process similar to thatdescribed in Example 9.

1-cyclopropyl-3-(diethoxycarbonyl)acetyl-6-fluoro-8-chloro-7-(cis-piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinolinehydrochloride;

1-cyclopropyl-3-nitroacetyl-6,8-difluoro-7- (cis-2,8-diazabicyclo4.3.0!nonane-3-methyl)-8-yl!-4-oxo-1,4-dihydroquinoline hydrochloride;and

1-cyclopropyl-3-(dimethoxycarbonyl)acetyl-6-fluoro-8-methoxy-7-(cis-piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinolinehydrochloride.

COMPARATIVE EXAMPLE 1 Preparation of 1-cyclopropyl-6-fluoro-8-methoxv-7-(cis-piperidinopyrrolidine)-8-yl!-4-oxo-1,4-dihydroquinoline-3-carboxylicacid

295 mg of1-cyclopropyl-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxo-3-carboxylic acidand 210 mg of cis-piperidinopyrrolidine dihydrochloride were treatedaccording to the same method as that of Example 5 to give 324 mg of theabove title compound (yield: 81%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 1.14-1.22(4H, m), 1.51-1.91(5H, m), 2.71-2.98(7H, m), 3.82(3H, s), 4.00(1H, m), 7.84(1H, d), 8.80(1H, s)

COMPARATIVE EXAMPLE 2 Preparation of 1-cyclopropyl-6.8-difluoro-7-(cis-piperidinopyrrolidine-3-methyl)-8-yl!-4-oxo-1,4-dihydroquinoline-3-carboxylicacid

283 mg of1-cyclopropyl-6,7,8-trifluoro-1,4-dihydroquinoline-4-oxo-3-carboxylicacid and 232 mg of cis-3-methylpiperidinopyrrolidine dihydrochloridewere treated according to the same method as that of Example 5 to give280 mg of the above title compound (yield: 71%).

    .sup.1 H-NMR(CDCl.sub.3, δ): 1.20(4H, m), 1.56-1.92(8H, m), 2.70-3.00(6H, m), 4.00(1H, m), 7.72(1H, d), 8.68(1H, s)

In vitro antibacterial activity test

The results of in vitro antibacterial activity test are shown in Tables1 and 2. The numbers in Tables represent the minimal inhibitoryconcentration (MIC, μg/ml) of the corresponding strains and MIC wasdetermined in accordance with the agar culture medium two-fold dilutionmethod by using a Mueller-Hinton agar.

Hoechst standard strains were used. The strains having 10⁷ CFU/ml wereinoculated on the culture medium, and the growth of the strains wasobserved after incubating them at 37° C. for 18 hours, in whichciprofloxacin was used as a control.

                  TABLE 1                                                         ______________________________________                                        In vitro antibacterial activity test (MIC, ug/ml)                                                                      Cipro-                               Strain       A       B       C     D     floxacin                             ______________________________________                                        Streptococcus pyogenes                                                                     0.391   0.781   0.781 1.563 3.125                                308A                                                                          Streptococcus pyogenes                                                                     0.098   0.195   0.391 0.391 0.781                                77A                                                                           Streptococcus faecium                                                                      0.098   0.195   0.391 0.391 0.781                                MD 8b                                                                         Staphylococcus aureus                                                                      0.025   0.098   0.098 0.195 0.195                                SG 511                                                                        Staphylococcus aureus                                                                      0.025   0.098   0.025 0.391 0.391                                285                                                                           Staphylococcus aureus                                                                      0.025   0.195   0.025 0.391 0.781                                503                                                                           Escherichia coli                                                                           <0.002  <0.025  <0.002                                                                              0.049 <0.002                               O 78                                                                          Escherichia coil                                                                           0.195   0.391   0.195 0.195 0.195                                DC 0                                                                          Escherichia coil                                                                           0.013   0.098   0.098 0.098 0.098                                DC 2                                                                          Escherichia coil                                                                           0.007   0.049   0.004 0.098 0.007                                TEM                                                                           Escherichia coil                                                                           0.025   0.049   0.025 0.098 0.007                                1507E                                                                         Pseudomonas aeruginosa                                                                     0.781   0.781   0.781 1.563 0.391                                9027                                                                          Pseudomonas aeruginosa                                                                     0.781   0.781   0.781 0.781 0.195                                1592E                                                                         Pseudomonas aeruginosa                                                                     0.781   1.563   0.781 0.781 0.195                                1771                                                                          Pseudomonas aeruginosa                                                                     0.195   0.391   0.391 0.391 0.049                                1771M                                                                         Salmonella typhimurium                                                                     <0.002  0.049   0.007 0.098 0.007                                Klebsiella aerogenes                                                                       <0.002  0.098   0.049 0.049 <0.002                               1082E                                                                         Klebsiella aerogenes                                                                       0.049   0.098   0.013 0.049 0.013                                1552E                                                                         Enterobacter cloacae                                                                       0.004   0.025   0.004 0.013 0.007                                P 99                                                                          Enterobacter cloacae                                                                       <0.002  0.013   <0.002                                                                              0.013 <0.002                               1321E                                                                         ______________________________________                                         A: The compound of Example 5                                                  B: The compound of Example 7                                                  C: The compound of Example 8                                                  D: The compound of Example 9                                             

What is claimed is:
 1. A trans-racemic mixture of a quinolone of Formula(I): ##STR13## wherein, X₁ represents hydrogen, amino, halogen, or loweralkyl;X₂ represents hydrogen or halogen; Y₁ and Y₂ each representshydrogen, or lower alkyl (C₁₋₃) group; R₁ represents a straight chain orcyclic lower alkyl group having 1 to 3 carbon atoms or a straight chainor cyclic lower alkyl group having 1 to 3 carbon atoms which issubstituted with a halogen atom, a phenyl group or a phenyl groupsubstituted with one or two halogen atoms; R₂ represents hydrogen, orlower alkyl: and A represents nitrogen atom or ##STR14## in which Yrepresents hydrogen, halogen, lower alkyl or alkoxy or together with R₁forms --CH₂ CH₂ CH₂ --, --CH₂ CH₂ CH(CH₃)--, --OCH₂ CH₂ --, --OCH₂CH(CH₃)--, --SCH₂ CH₂ --, or --SCH₂ CH(CH₃)--.
 2. A trans-racemicmixture of claim 1 of Formula (I) selected from the group consistingof;1-cyclopropyl-6-fluoro-7-(trans-piperidinopyrrolidine)-8-yl!-8-chloro-1,4-dihydroquinoline-4-oxo-3-carboxylicacid, 1-cyclopropyl-6,8-difluoro-7-(trans-piperidinopyrrolidine)-8-yl!-1,4-dihydroquinoline-4-oxo-3-carboxylicacid, 1-cyclopropyl-6-fluoro-7-(trans-piperidinopyrrolidine)-8-yl!-1,4-dihydroquinoline-4-oxo-3-carboxylicacid, 1-cyclopropyl-5-amino-6,8-difluoro-7-(trans-piperidinopyrrolidine)-8-yl!-1,4-dihydroquinoline-4-oxo-3-carboxylicacid, 1-cyclopropyl-5-methyl-6-fluoro-7-(trans-piperidinopyrrolidine)-8-yl!1,4-dihydroquinoline-4-oxo-3-carboxylicacid, 1-cyclopropyl-6-fluoro-7-(trans-piperidinopyrrolidine)-8-yl!-8-methoxy-1,4-dihydroquinoline-4-oxo-3-carboxylicacid, 1-cyclopropyl-6-fluoro-7- (trans-piperidinopyrrolidine)-8-yl!-1,4-dihydro-4-oxo-1,8-naphthyridin-3-carboxylic acid,1-(2,4-difluorophenyl)-6-fluoro-7-(trans-piperidinopyrrolidine)-8-yl!-1,4-dihydro-4-oxo-1,8-naphthyridin-3-carboxylicacid, 9-fluoro-10-(trans-piperidinopyrrolidine)-8-yl!-2,3-dihydro-3-methyl-7-oxo-7H-pyrido1,2,3-de! 1,4!-benzooxazine-6-carboxylic acid,1-cyclopropyl-6,8-difluoro-7- (trans-3-methyl-2,8-diazabicyclo4.3.0!nonane)-8-yl!-1,4-dihydroquinoline-4-oxo-3-carboxylic acid,1-cyclopropyl-6-fluoro-7- (trans-3-methyl-2, 8-diazabicyclo4.3.0!nonane)-8-yl!-8-chloro-1,4-dihydroquinoline-4-oxo-3-carboxylicacid, 1-cyclopropyl-5-amino-6,8-difluoro-7-(trans-3-methyl-2,8-diazabicyclo4.3.0!nonane)-8-yl!-1,4-dihydroquinoline-4-oxo-3-carboxylic acid,-cyclopropyl-5-methyl-6-fluoro-7- (trans-3-methyl-2,8-diazabicyclo4.3.0!nonane)-8-yl!-1,4-dihydroquinoline-4-oxo-3-carboxylic acid,1-cyclopropyl-6-fluoro-7- (trans-3-methyl-2,8-diazabicyclo4.3.0!nonane)-8-yl!-8-methoxy-1,4-dihydroquinoline-4-oxo-3-carboxylicacid, 1-cyclopropyl-6-fluoro-7- (trans-3-methyl-2, 8-diazabicyclo4.3.0)!nonane)-8-yl!-1,4-dihydro-4-oxo-1,8-naphthyridin-3-carboxylicacid, 9-fluoro-10- (trans-3-methyl-2,8-diazabicyclo4.3.0!nonane)-8-yl!-2,3-dihydro-3-methyl-7-oxo-7H-pyrido 1,2,3-de!1,4!-benzooxazine-6-carboxylic acid.
 3. A process for preparing atrans-racemic mixture of Formula (I) of claim 1 comprising condensingoptionally protected trans-2,8-diazabicyclo 4.3.0!nonane derivatives offormula (II) with the compound of formula (VI-1) in a solvent, in thepresence of an inorganic base such as calcium carbonate and the like oran organic base such as diazabicyclo 5.4.0!undecene (DBU), pyridine,triethylamine and the like: ##STR15## wherein, X₁, X₂, Y₁, Y₂, R₁, R₂,and A are the same as defined in claim 1 or R₂ is a protecting group,and thereafter optionally deprotecting.
 4. A pharmaceutical compositionwhich contains a trans-racemic mixture or pharmaceutically acceptablesalt thereof Formula (I) according to claim 1, as an active ingredientin an effective amount.
 5. A method for the treatment of bacterialinfection characterized in that a pharmaceutical composition comprisinga trans-racemic mixture or pharmaceutically acceptable salt thereofaccording to Formula (I) is administered to a host in need of suchtreatment in the therapeutically effective amount.